Related Experiment Video
Updated: Aug 11, 2026
11:38
Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
Hgs physically interacts with Smad5 and attenuates BMP signaling
Jochen Haag1, Susan Chubinskaya, Thomas Aigner
1Osteoarticular and Arthritis Research, Department of Pathology, Friedrich-Alexander University of Erlangen-Nuremberg, Krankenhausstr. 8-10, D-91054 Erlangen, Germany.
Experimental Cell Research
|March 7, 2006
Summary
Researchers identified Hgs as a novel inhibitor of bone morphogenetic protein (BMP) signaling in adult cartilage. Reduced Hgs expression in osteoarthritic chondrocytes may link to altered BMP pathway activity.
Area of Science:
- Biochemistry
- Cell Biology
- Orthopedics
Background:
- Bone morphogenetic proteins (BMPs) are crucial for cartilage development and differentiation.
- Emerging evidence suggests BMPs may also play a role in adult articular cartilage maintenance and repair.
- Understanding BMP signaling pathways in adult cartilage is essential for regenerative medicine.
Purpose of the Study:
- To identify novel interactors of Smad5, a key mediator of BMP signaling, in human adult cartilage.
- To investigate the role of identified interactors in regulating BMP-dependent gene expression.
- To explore the potential involvement of these factors in osteoarthritis pathogenesis.
Main Methods:
- Construction of a cDNA expression library from human adult cartilage.
- Identification of Hgs (HGS) as a Smad5 interactor using yeast two-hybrid screening.
- Confirmation of Hgs-Smad5 interaction via coimmunoprecipitation in cell lines (293 EBNA, T/C-28a2).
- Assessment of Hgs effects on BMP-responsive reporter gene activity.
- Analysis of Hgs expression levels in osteoarthritic chondrocytes.
Main Results:
- Hgs was identified as a novel Smad5-interacting protein in human adult cartilage.
- Coimmunoprecipitation confirmed the interaction between Hgs and Smad5.
- Overexpression of Hgs attenuated BMP-induced transcriptional responses, indicating an inhibitory role.
- Osteoarthritic chondrocytes exhibited reduced Hgs expression compared to healthy controls.
- BMP signaling was shown to suppress Hgs expression.
Conclusions:
- Hgs acts as an inhibitor of BMP signaling in adult chondrocytes.
- The observed decrease in Hgs expression in osteoarthritic chondrocytes may contribute to altered BMP pathway responsiveness.
- These findings suggest a potential link between Hgs, BMP signaling, and osteoarthritis.
- Hgs represents a potential therapeutic target for cartilage repair and osteoarthritis treatment.
Related Concept Videos
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
02:33Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:22Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...